The major aim of the proposed reach is to determine the physiologic bases for the aciduric character of cariogenic oral streptococci. Our fundamental assumption is that the abilities of cariogenic bacteria to carry out glycolysis at environmental pH values as low as 4.0 are not related to inherent acid resistance of glycolytic enzymes but rather to the membrane functions of proton extrusion through the membrane ATPase and proton exclusion by the lipoidal barriers of the membrane. The proposal focuses on aciduric strains of Streptoccus muttans and a less aciduric strain of Streptococcus sanguis. Determinations will be made of the capacities of the test bacteria in acid environments to develop and maintain Delta pH across the cell membrane with the cytoplasm alkaline in relation to the suspending medium. Assessments will be made also of the importance of Delta pH and the maintenance of a relatively alkaline cytoplasm for glycolysis. We shall attempt to identify the specific steps in sugar uptake and metabolism that are most sensitive to cytoplasmic acidification. The roles of the proton extruding and proton excluding functions of the membrane for development and maintenance of Delta pH will be investigated in conjunction with studies of the actions of fluoride and other weak acids in enhancing transmembrane proton movements and thereby reducing acidurance. Attempts will be made to isolate acid-tolerant and acid-sensitive variants or mutants and to determine the physiological bases for tolerance and sensitivity. In essence, the proposed program involves primarily the application of modern knowledge and technology gained from studies of the acid-base physiology of bacteria such as Streptococcus faecalis and Escherichia coli to the oral streptococci which cause so much annoyance, misery and expense for the human population because of their abilities to reduce the pH of dental plaque below the critical value for dissolution of enamel hydroxyapatite.